Bio Sci 37 Midterm 3

What is the most common mental disorder

substance abuse

Statistics for substance abuse disorder

In the US —> 8 to 10% of people 12 years of age or older, or 20-22 million people, are addicted to alcohol and drugs

How many deaths is responsible for how many deaths worldwide

11.8 million each year (accounts for a fifth of all deaths around the world, higher than cancer-related deaths)

Reasons people use legal/illegal drugs

• pleasurable effects

• alteration of mental state

• improve performance

• self-medication for a mental disorder

Repeated use of drugs leads to what?

addiction

Will all people develop drug addiction after several exposures

no

Individual vulnerability to drug addiction is linked to what

environmental and genetic factors

Is drug addiction polygenic

yes —> hundreds of genetic variations combined result in variable vulnerability

How do environmental factors and genetic factors intertwine (substance use disorder)

several environmental factors interact with individual genetic background

Risk factors of substance use disorder

• aggressive behavior in childhood

• lack of parental support

• low peer refusal skills

• drug experimentation

• availability of drugs at school

• community poverty

Protective factors of substance use disorder

• self-efficacy (belief in self-control)

• parental monitoring and support

• positive relationships

• good grades

• school anti-drug policies

• neighborhood resources

Factors that increase risk of addiction

• home and family

  • genetics and epigenetics

  • lack of family involvement (parental bond/supervision)

  • home environment (especially during childhood)

• presence of mental disorders

• peer and school

  • school performance

  • social skills

• early use

  • effect on developing brain

  • early social and biological risk factors

• taking a highly addictive drug

  • route of administration

DNA methylation

add a methyl group to DNA —> process alters expression of genes by activating or repressing them

Histone modification

epigenetic factors can attach to histone tails and affect how tightly wound DNA is around the histone; DNA that is more tightly wound – not easily activated and vice versa

Other types of epigenetic modifications

• acetylation

• phosphorylation

• ubiquitylation

• sumoylation

How does abusing drugs affect histone acetylation in the brain?

1. increases epigenetic alteration

   • alter how tightly DNA is packed

   • leads to increased acetylation —> certain genes = more active

2. increased expression of transcription factors such as c-Fos and FosB

   • ΔFosB overexpression has been implicated in addictions to many drugs of abuse

   • ΔFosB functions as molecular switch that
     converts acute drug responses into stable adaptations that
     contribute to the long-term neural and behavioral plasticity that
     underlies addiction

3. modifications in brain structure and function

4. synaptic remodeling

What are histones

• proteins that DNA wraps around —> together they form chromatin, which controls if genes are accessible or hidden

• if DNA is tightly wrapped around them —> genes are hidden and cannot be turned on

What are epigenetics

• changes that affect gene activity without changing the DNA sequence itself

• e.g. histone acetylation —> loosens the DNA and allows genes to turn on

What does it mean to be addicted

a compulsive drive to take a drug or engage in drug seeking behavior —> w/ an impaired ability to control the urge to take the drug despite serious consequences

What does addiction refer to

drug (or substance) dependence

What physical dependence on drugs refer to

withdrawal symptoms when no longer taking the drug —> effects = different from those that underlie addiction

Substance use disorder

recurrent use drugs that causes clinically and functionally significant
impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home

Classifications of substance use disorders

depends on level of severity:

• mild (2-3 symptoms)

• moderate (4-5)

• severe (6+)

Addiction

a term used to indicate the most severe, chronic stage of substance-use disorder, in which
there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug

What are the 11 diagnostic criteria for SUD

1. Taking the substance in larger amounts or for longer than you're meant to

2. Wanting to cut down or stop using the substance but not managing to

3. Spending a lot of time getting, using, or recovering from use of the substance

4. Cravings and urges to use the substance

   • IMPAIRED CONTROL

5. Not managing to do what you should at work, home, or school because of substance use

6. Continuing to use, even when it causes problems in relationships

7. Giving up important social, occupational, or recreational activities because of substance use

   • SOCIAL IMPAIRMENT

8. Using substances again and again, even when it puts you in danger

9. Continuing to use, even when you know you have a physical or psychological problem that could have been caused or made worse by the substance

   • RISKY USE

10. Needing more of the substance to get the effect you want (tolerance)

11. Development of withdrawal symptoms, which can be relieved by taking more of the substance

    • PHARMACOLOGICAL DEPENDENCE

    
    

Other criteria for SUD (tolerance)

• a need for increased amounts to achieve a high

• markedly diminished effect with con’t use

Other criteria for SUD (withdrawal symptoms)

• psychological and/or physical syndrome caused by the abrupt cessation of the use of a drug

• taking the substance often in larger amounts or over a longer period than was intended

• having a persistent desire or unsuccessful efforts to cut down or control substance use
  

Is addiction a disease of the brain

yes —> abnormal behavior is a result of dysfunction in the brain

• studies show that repeated drug use leads to long-term changes in brain regions responsible for motivation, reward, and inhibitory control in addicted individuals (seen in PET scans of glucose metabolism)

• initial drug use may be voluntary BUT once addiction sets in, control processes are disrupted

10 classes of drugs

1. Alcohol

2. Caffeine

3. Cannabis

4. Hallucinogens

5. Inhalants

6. Opioids

7. Sedatives

8. Hypnotics, or anxiolytics

9. Stimulants (including amphetamine-type substances, cocaine, and other stimulants)

10. Tobacco

How are the classes of drugs similar and different

• the pharmacological mechanisms for each class of drug are different

• activation of the reward system is similar across substances in producing feelings of pleasure or euphoria

Fentanyl

• synthetic opioid similar to morphine but 50-100 times more potent

• it is a prescription drug used to treat severe pain, especially after surgery

• involved in most overdose deaths in the US

Where is fentanyl made and sold

• made in labs and sold illegally as powder

• dropped into blotter paper, put in eye droppers and nasal sprays, made into pills that look like prescription opioids

• drug dealers mix fentanyl w/ drugs (heroin, coke, meth, and MDMA b/c it takes very little to produce high w/ fent —> cheaper)

Why is fentanyl so dangerous

b/c people don’t realize they are taking it most of the time —> consuming stronger opioids than what their body can handle

How does fentanyl work

• like heroin and morphine —> binds to opioid receptors (found in areas of the brain that control pain and emotions)

Treatments for fentanyl addiction

• medication combined with behavioral therapies

• meds:

  • buprenorphine and methadone work by
    binding to the same opioid receptors in the brain as
    fentanyl, reducing cravings and withdrawal symptoms

  • another medicine, naltrexone, blocks opioid receptors
    and prevents fentanyl from having an effect

The reward system

group of brain structures and neural pathways that are responsible for:

• craving for reward and motivation

• associative learning (pos. reinforcement)

• emotions associated w/ pleasure

What does the reward system do

motivate animals to approach stimuli or engage in behavior that inc. fitness (sex, energy-dense foods, etc)

What does drug addiction do to reward system

over-activate or hijack the reward circuit, leading to compulsive substance-seeking behavior

The three main brain regions involved in reward system